During the transition to adulthood, emerging adults may experience new geographic distance separating them from their siblings. Digital leisure is common among emerging adults and may serve as a tool ...for maintaining relationship quality across geographic distance. Using qualitative data, we created individual digital leisure diversity scores for four categories of digital leisure identified from a constructed taxonomy. The sample included 185 college-attending emerging adults (M
age
= 20.1, 64.3% male). Analysis of variance indicated dyadic gender differences in social media and gaming. Digital leisure diversity was associated with greater levels of affective and cognitive sibling relationship quality, regardless of sibling dyad gender. The association between digital leisure diversity and cognitive relationship quality was significant for participants who lived closer to their sibling. During the transition to adulthood when new geographic separation is common, digital leisure shows potential as a compensatory activity that may help siblings maintain relationship quality.
As in mammals, Drosophila circadian clock neurons display rhythms of activity with higher action potential firing rates and more positive resting membrane potentials during the day. This rhythmic ...excitability has been widely observed but, critically, its regulation remains unresolved. We have characterized and modelled the changes underlying these electrical activity rhythms in the lateral ventral clock neurons (LNvs). We show that currents mediated by the voltage‐gated potassium channels Shaw (Kv3) and Shal (Kv4) oscillate in a circadian manner. Disruption of these channels, by expression of dominant negative (DN) subunits, leads to changes in circadian locomotor activity and shortens lifespan. LNv whole‐cell recordings then show that changes in Shaw and Shal currents drive changes in action potential firing rate and that these rhythms are abolished when the circadian molecular clock is stopped. A whole‐cell biophysical model using Hodgkin‐Huxley equations can recapitulate these changes in electrical activity. Based on this model and by using dynamic clamp to manipulate clock neurons directly, we can rescue the pharmacological block of Shaw and Shal, restore the firing rhythm, and thus demonstrate the critical importance of Shaw and Shal. Together, these findings point to a key role for Shaw and Shal in controlling circadian firing of clock neurons and show that changes in clock neuron currents can account for this. Moreover, with dynamic clamp we can switch the LNvs between morning‐like and evening‐like states of electrical activity. We conclude that changes in Shaw and Shal underlie the daily oscillation in LNv firing rate.
We report the first counts of faint submillimetre galaxies (SMGs) in the 870-μm band derived from arcsecond-resolution observations with the Atacama Large Millimeter Array (ALMA). We have used ALMA ...to map a sample of 122 870-μm-selected submillimetre sources drawn from the 0
5×0
5 the Large Apex BOlometer CAmera (LABOCA) Extended Chandra Deep Field South submillimetre survey (LESS). These ALMA maps have an average depth of σ870 μm ∼ 0.4 mJy, some approximately three times deeper than the original LABOCA survey and critically the angular resolution is more than an order of magnitude higher, FWHM of ∼1.5 arcsec compared to ∼19 arcsec for the LABOCA discovery map. This combination of sensitivity and resolution allows us to precisely pinpoint the SMGs contributing to the submillimetre sources from the LABOCA map, free from the effects of confusion. We show that our ALMA-derived SMG counts broadly agree with the submillimetre source counts from previous, lower resolution single-dish surveys, demonstrating that the bulk of the submillimetre sources are not caused by blending of unresolved SMGs. The difficulty which well-constrained theoretical models have in reproducing the high surface densities of SMGs, thus remains. However, our observations do show that all of the very brightest sources in the LESS sample, S
870 μm 12 mJy, comprise emission from multiple, fainter SMGs, each with 870-μm fluxes of 9 mJy. This implies a natural limit to the star formation rate in SMGs of 103 M yr−1, which in turn suggests that the space densities of z > 1 galaxies with gas masses in excess of ∼5 × 1010 M is <10−5 Mpc−3. We also discuss the influence of this blending on the identification and characterization of the SMG counterparts to these bright submillimetre sources and suggest that it may be responsible for previous claims that they lie at higher redshifts than fainter SMGs.
We study the radio properties of 706 submillimeter galaxies (SMGs) selected at 870 m with the Atacama Large Millimeter Array from the SCUBA-2 Cosmology Legacy Survey map of the Ultra Deep Survey ...field. We detect 273 SMGs at >4 in deep Karl G. Jansky Very Large Array 1.4 GHz observations, of which a subset of 45 SMGs are additionally detected in 610 MHz Giant Metre-Wave Radio Telescope imaging. We quantify the far-infrared/radio correlation (FIRRC) through parameter qIR, defined as the logarithmic ratio of the far-infrared and radio luminosity, and include the radio-undetected SMGs through a stacking analysis. We determine a median qIR = 2.20 0.03 for the full sample, independent of redshift, which places these z ∼ 2.5 dusty star-forming galaxies 0.44 0.04 dex below the local correlation for both normal star-forming galaxies and local ultra-luminous infrared galaxies (ULIRGs). Both the lack of redshift evolution and the offset from the local correlation are likely the result of the different physical conditions in high-redshift starburst galaxies, compared to local star-forming sources. We explain the offset through a combination of strong magnetic fields (B 0.2 mG), high interstellar medium (ISM) densities and additional radio emission generated by secondary cosmic rays. While local ULIRGs are likely to have similar magnetic field strengths, we find that their compactness, in combination with a higher ISM density compared to SMGs, naturally explains why local and high-redshift dusty star-forming galaxies follow a different FIRRC. Overall, our findings paint SMGs as a homogeneous population of galaxies, as illustrated by their tight and nonevolving far-infrared/radio correlation.
Abstract
We present Atacama Large Millimeter/submillimeter Array (ALMA) 2 mm continuum observations of a complete and unbiased sample of 99 870
μ
m selected submillimeter galaxies (SMGs) in the ...Extended Chandra Deep Field South (ALESS). Our observations of each SMG reach average sensitivities of 53
μ
Jy beam
−1
. We measure the flux densities for 70 sources, for which we obtain a typical 870
μ
m-to-2 mm flux ratio of 14 ± 5. We do not find a redshift dependence of this flux ratio, which would be expected if the dust emission properties of our SMGs were the same at all redshifts. By combining our ALMA measurements with existing Herschel/SPIRE observations, we construct a (biased) subset of 27 galaxies for which the cool dust emission is sufficiently well sampled to obtain precise constraints on their dust properties using simple isothermal models. Thanks to our new 2 mm observations, the dust emissivity index is well constrained and robust against different dust opacity assumptions. The median dust emissivity index of our SMGs is
β
≃ 1.9 ± 0.4, consistent with the emissivity index of dust in the Milky Way and other local and high-redshift galaxies, as well as classical dust-grain model predictions. We also find a negative correlation between the dust temperature and
β
, similar to low-redshift observational and theoretical studies. Our results indicate that
β
≃ 2 in high-redshift dusty star-forming galaxies, implying little evolution in dust-grain properties between our SMGs and local dusty galaxy samples, and suggesting that these high-mass and high-metallicity galaxies have dust reservoirs driven by grain growth in their interstellar medium.
Schizophrenia shows high heritability and several of the genes associated with this disorder are involved in calcium (Ca
) signalling and synaptic function. One of these is the Rab-3 interacting ...molecule-1 (RIM1), which has recently been associated with schizophrenia by Genome Wide Association Studies (GWAS). However, its contribution to the pathophysiology of this disorder remains unexplored. In this work, we use Drosophila mutants of the orthologue of RIM1, Rim, to model some aspects of the classical and non-classical symptoms of schizophrenia. Rim mutants showed several behavioural features relevant to schizophrenia including social distancing and altered olfactory processing. These defects were accompanied by reduced evoked Ca
influx and structural changes in the presynaptic terminals sent by the primary olfactory neurons to higher processing centres. In contrast, expression of Rim-RNAi in the mushroom bodies (MBs), the main memory centre in flies, spared learning and memory suggesting a differential role of Rim in different synapses. Circadian deficits have been reported in schizophrenia. We observed circadian locomotor activity deficits in Rim mutants, revealing a role of Rim in the pacemaker ventral lateral clock neurons (LNvs). These changes were accompanied by impaired day/night remodelling of dorsal terminal synapses from a subpopulation of LNvs and impaired day/night release of the circadian neuropeptide pigment dispersing factor (PDF) from these terminals. Lastly, treatment with the commonly used antipsychotic haloperidol rescued Rim locomotor deficits to wildtype. This work characterises the role of Rim in synaptic functions underlying behaviours disrupted in schizophrenia.
Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are ...required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC.
Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature.
A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone.
We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.
A phase I study was conducted to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of a novel purine nucleoside, nelarabine, a soluble prodrug of ...9-beta-D-arabinosylguanine (araG; Nelarabine), in pediatric and adult patients with refractory hematologic malignancies.
Between April 1994 and April 1997, 93 patients with refractory hematologic malignancies were treated with one to 16 cycles of study drug. Nelarabine was administered daily, as a 1-hour intravenous infusion for 5 consecutive days, every 21 to 28 days. First-cycle pharmacokinetic data, including plasma nelarabine and araG levels, were obtained on all patients treated. Intracellular phosphorylation of araG was studied in samples of leukemic blasts from selected patients.
The MTDs were defined at 60 mg/kg/dose and 40 mg/kg/dose daily x 5 days in children and adults, respectively. Dose-limiting toxicity (DLT) was neurologic in both children and adults. Myelosuppression and other significant organ toxicities did not occur. Pharmacokinetic parameters were similar in children and adults. Accumulation of araGTP in leukemic blasts was correlated with cytotoxic activity. The overall response rate was 31%. Major responses were seen in patients with T-cell malignancies, with 54% of patients with T-lineage acute lymphoblastic leukemia achieving a complete or partial response after one to two courses of drug.
Nelarabine is a novel nucleoside with significant cytotoxic activity against malignant T cells. DLT is neurologic. Phase II and III trials in patients with T-cell malignancies are encouraged.
Attempts to account for observed variation in the degree of reproductive skew among cooperative breeders have usually assumed that subordinate breeding has fitness costs to dominant females. They ...argue that dominant females concede reproductive opportunities to subordinates to retain them in the group or to dissuade them from challenging for the dominant position or that subordinate females breed where dominants are incapable of controlling them. However, an alternative possibility is that suppressing subordinate reproduction has substantive costs to the fitness of dominant females and that variation in these costs generates differences in the net benefits of suppression to dominants which are responsible for variation in the frequency of subordinate breeding that is not a consequence of either reproductive concessions or limitations in dominant control. Here, we show that, in wild Kalahari meerkats (Suricata suricatta), the frequency with which dominants evict subordinates or kill their pups varies with the costs and benefits to dominants of suppressing subordinate breeding, including the dominants' reproductive status, the size of their group, and the relatedness of subordinates. We review evidence from other studies that the suppression of reproduction by subordinates varies with the likely costs of subordinate breeding to dominants.
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